中国药理学通报Issue(7)：1019-1022,1023,5.DOI:10.3969/j.issn.1001-1978.2015.07.026
比格犬体内FGFC1药物代谢动力学特征及组织分布的研究
Pharmacokinetics and tissue distribution of FGFC1,a novel marine fibrinolytic compound in Beagle dogs
摘要
Abstract
Aim To detect the concentration of the no-vel marine fibrinolytic compound FGFC1 ( fungi fi-brinolytic compound 1 ) on Beagle dogs ’ plasma and tissue by high performance liquid chromatography ( HPLC) , and also to investigate the pharmacokinetics and tissue distribution in Beagle dogs with intravenous injection, and to evaluate the FGFC1 into medicinal. Methods Chromatographic column: HP-C18 ( 4. 6 mm × 250 mm,5 μm); the column temperature was 40℃;the mobile phase was acetonitrile -0. 1% triflu-oroacetic acid gradient elute, the flow rate of 1 mL· min-1; the ultraviolet detection wavelength was 265 nm. The dog plasma samples were collected at different intervals after intravenous injection of three different doses (7. 5, 5. 0, 2. 5 mg·kg-1 ) of FGFC1, and the concentration of FGFC1 in plasma and tissue was deter-mined by HPLC method for estimating pharmacokinetic parameters and tissue distribution. Results The pa-rameters of 7. 5, 5. 0, 2. 5 mg·kg-1 were as follows:its elimination half-life ( T1/2β) was ( 49. 035 ± 2. 171 ) , ( 48. 422 ± 2. 113 ) and ( 48. 811 ± 2. 372 ) min, respectively;the peak concentration was (56. 48 ± 6. 23 ) , ( 48. 63 ± 5. 53 ) , ( 13. 64 ± 2. 76 ) mg · L-1 , respectively;clearance rate ( CL ) was ( 0. 0062 ± 0. 0004 ) , ( 0. 0071 ± 0. 0008 ) and ( 0. 0092 ± 0. 0006) L·min-1 ·kg-1 , respectively; mean reten-tion time ( MRT ) was ( 28. 17 ± 1. 16 ) , ( 26. 23 ± 0. 35) and (28. 66 ± 0. 84) min, respectively. Tissue distribution revealed that FGFC1 could quickly distrib-uted into the heart, liver, spleen, lung, kidney, intes-tine, stomach, brain, intestine, testicle, urine and fe-ces. Interestingly, the highest drug (FGFC1) concen-tration level was detected in the liver. Conclusions The above study shows a good pharmacokinetic profile as well as a good tissue distribution, indicating a drug-gable nature of the structure. Therefore, we consider that FGFC1 is promising for further study.关键词
FGFC1/药代动力学特征/组织分布/高效液相色谱/比格犬/血药浓度Key words
FGFC1/pharmacokinetics/tissue distri-bution/HPLC/Beagle dogs/plasma concentration分类
医药卫生引用本文复制引用
王格,吴文惠,王小雨,张朝燕,包斌..比格犬体内FGFC1药物代谢动力学特征及组织分布的研究[J].中国药理学通报,2015,(7):1019-1022,1023,5.基金项目
国家高技术研究发展计划资助项目( No 2011AA09070109) （ No 2011AA09070109）
国家自然科学基金资助项目( No 81341082) （ No 81341082）
上海海洋大学科技发展专项基金资助项目(No 14200069) （No 14200069）
